α-Tertiary Primary Amine Synthesis via Photocatalytic C(sp³)–H Aminoalkylation

Abstract

Facile access to sterically hindered α-tertiary primary amines via photocatalytic radical coupling of native C(sp 3 )−H substrates with N-unsubstituted ketimines is reported. LiBr was used as a hydrogen atom transfer reagent to cleave C(sp 3 )−H bonds to get alkyl radicals. The in situ-generated HBr can then serve as a Bronsted acid to activate N-unsubstituted ketimines readily for single-electron reduction to deliver α-amino radicals. As a consequence, radical−radical coupling affords primary amines with a congested α-tertiary substituent. This reaction is highlighted by simple and mild conditions, 100% atomeconomy, and broad hydrocarbon substrate scope for benzyl ethers, cyclic ethers, benzyl alcohols, alkylarenes, and carbocycles.

Photoredox-Catalyzed Radical–Radical Cross-Coupling of α-Ketoesters with Ethers: Access to Sterically Hindered α-Hydroxy Esters

“…Next, fluorescence quenching experiments showed that only n Bu 4 NBr can significantly quench the excited state of Ir­[dF­(CF 3 )­ppy] 2 (dtbbpy)­PF 6 (Figures S3–S5). In addition, the results of CV measurements (Figures S6 and S7) indicated that n Bu 4 NBr (the onset potential for oxidation is approximately +0.66 V vs SCE in MeCN) can be oxidized by Ir­[dF­(CF 3 )­ppy] 2 (dtbbpy)­PF 6 * ( E ox,1/2 = +1.21 vs SCE in MeCN), and 1a (the onset potential for reduction is approximately −1.16 V vs SCE in MeCN) can be reduced by the reduced form of the photocatalyst Ir II ( E red,1/2 = −1.37 V vs SCE in MeCN).…”

Photoredox Enabled Defluorinative Benzylation of Trifluoromethyl Alkenes with Alkylarenes

“…While the transition-metal-catalyzed C­(sp 2 )–H functionalization reactions have been extensively explored, the functionalization of C­(sp 3 )–H bonds is more challenging due to the low reactivity and selectivity. In this context, benzylic C–H bonds are ubiquitous in naturally occurring molecules, pharmaceuticals, agrochemicals, and functional materials; therefore, it has attracted extensive interest to develop diverse strategies for the direct functionalization of benzylic C–H bonds . Especially, alkylarenes are abundant, readily available chemical feedstocks, and they have been used as versatile synthons in organic synthesis.…”